Comparison of the Expression and Immunogenicity of Wild-Type and Sequence-Modified HIV-1 gag Genes in a Recombinant Sendai Virus Vector

Efficient expression of HIV-1 structural gene involves regulation by viral Rev and Rev-responsive elements (RRE). Messenger RNAs of wild-type HIV-1 structural genes are either retained in the nucleus or degraded rapidly in the absence of Rev/RRE; therefore little protein can be expressed. Modifying HIV-1 genes is an excellent approach to circumvent this problem, but it is a laborious and costly process. Using certain vectors to deliver wild-type genes may be a promising approach. In this study, the wild-type and modified gag genes, derived from Chinese HIV-1 isolates, were separately constructed in both plasmid DNA and recombinant Sendai virus vectors (rSeV). The expression and immunogenicity of the wild-type and modified gag genes were compared. The results showed that efficient expression of the modified gag gene could be achieved by transfection with DNA and infection with rSeV, but the efficient expression of wild-type gag could only be achieved by rSeV. In addition, the rSeV expressing wild-type gag elicited similar Gag-specific immune responses with modified gag in both SeV/SeV and DNA-prime/rSeV-boost schemes. However, SeV/SeV failed to produce Gag-specific responses as robust as DNA/rSeV. Then the SeV-specific humoral and cellular immune responses were evaluated just before the second rSeV vaccine immunization. It was found that anti-SeV neutralizing antibody was very low but the SeV-specific cellular response was strong. Efficient expression of wild-type HIV-1 structural genes may make the SeV vector a useful tool for the HIV-1 vaccine research, but the strong SeV-specific cellular immune responses may impair the efficacy of SeV-SeV vaccination scheme.